De Novo Sequencing of Nonribosomal Peptides

While nonribosomal peptides (NRPs) are of tremendous pharmacological importance, there is currently no technology capable of highthroughput sequencing of NRPs. Difficulties in sequencing NRPs slow down the progress in elucidating the non-ribosomal genetic code and negatively affect various screening programs aimed at the discovery of natural compounds of medical importance. We propose to employ multistage mass-spectrometry (MS) for the data acquisition, followed by alignment-based heuristic algorithms for data analysis. Since mass spectrometry based analysis of NRPs is fast and inexpensive, this approach opens the possibility of high-throughput sequencing of many unknown NRPs accumulated in large screening programs.